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FIBROMYALGIA,CHRONIC FATIGUE SYNDROME AND RELATED CENTRAL SENSITIVITY SYNDROMES (CSS)A PRIMARY CARE TOOLKIT COMPLEX CHRONIC DISEASES PROGRAMBC WOMEN’S HOSPITAL

Ric Arseneau, MD FRCPC MA(Ed) MBA FACP CGPClinical ProfessorDivision of General Internal MedicineSt. Paul's Hospital & BC Women’s HospitalDirector of Program PlanningComplex Chronic Diseases ProgramUniversity of British Columbia

No Conflicts of Interest to Declare

Psychological / PsychiatricNot realNothing you can doFrustrating / unsatisfying Free-association exercise with housestaff

MEDICALLY UNEXPLAINEDPHYSICAL SYMPTOMS(MUPS)IS IT REAL ?

IS IT RARE ?

5 OVERLAPPING GROUPS

Pain

Unexplained Symptoms

Sleep Problems

Fatigue

Brain Fog

GutCNSAutonomic

Pain Research and TreatmentVolume 2012, Article ID 584573, 8 pagesdoi:10.1155/2012/584573

Review ArticleThe Prevalence of Fibromyalgia in Other Chronic Pain Conditions

Muhammad B. Yunus

Section of Rheumatology, Department of Medicine, University of Illinois College of Medicine at Peoria, One Illini Drive,Peoria, IL 61605, USA

Correspondence should be addressed to Muhammad B. Yunus, [email protected]

Received 3 May 2011; Accepted 15 August 2011

Academic Editor: Mary-Ann Fitzcharles

Copyright © 2012 Muhammad B. Yunus. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Central sensitivity syndromes (CSS) include fibromyalgia syndrome (FMS), irritable bowel syndrome, temporomandibulardisorder, restless legs syndrome, chronic fatigue syndrome, and other similar chronic painful conditions that are based on centralsensitization (CS). CSS are mutually associated. In this paper, prevalence of FMS among other members of CSS has been described.An important recent recognition is an increased prevalence of FMS in other chronic pain conditions with structural pathology, forexample, rheumatoid arthritis, systemic lupus, ankylosing spondylitis, osteoarthritis, diabetes mellitus, and inflammatory boweldisease. Diagnosis and proper management of FMS among these diseases are of crucial importance so that unwarranted use ofsuch medications as corticosteroids can be avoided, since FMS often occurs when RA or SLE is relatively mild.

1. Introduction: Historical Overview and theImportance of Nomenclatures

The fact that fibromyalgia syndrome (FMS) is associated withseveral similar conditions without structural pathology wasfirst reported in a controlled study in 1981 [1], followingwhich a conceptual model was proposed with a Venn dia-gram, showing the mutual overlaps in these syndromes [2].Since then, a large number of studies have confirmed theseassociations, compared with both healthy controls as well asdiseases with structural (the so-called “organic”) pathology(DWSP) [3, 4]. (Although there are structural changes,e.g., decreased hippocampus and gray matter volume insome CSS conditions, these changes seem to result fromprolonged central sensitization (CS) and will be discussedat the end.) These overlapping conditions are collectivelyknown as central sensitivity syndromes (CSS) [5–8], since CSis the common binding glue between them. The term CSSwas first coined in 2000 [5] and has been reviewed [5–8]. We[6] and others [9] have described mutual associations amongthe CSS conditions.

In contrast to association of FMS with other CSS mem-bers, association of FMS with DWSP was reported somewhatlater [10] and more frequently only in recent years. Wolfe and

Cathey were the first to recognize the association of FMS withrheumatoid arthritis (RA) [10]. Although they were called“secondary fibrositis,” these were cases of concomitant FMSwith typical symptoms and multiple tender points (TP) inassociation with RA. The diagnosis of FMS in the pre-1990ACR criteria era was made on the characteristic symptoms ofFMS as well as many tender points [10].

What’s in a name? Asked Shakespeare rhetorically inRomeo and Juliet. My own answer is “A lot.” A name shouldbe meaningful, tell the gist of the topic, and must not distortthe underlying truth, recognizing that scientific truth is notcarved in rock and does change over time. In this discourse, Ishall use the terms syndrome, illness, condition, and diseasesynonymously. Further, since the term fibromyalgia impliesnothing more than pain as has been discussed by Fitzcharlesand Yunus in this issue of the journal, I prefer the term“fibromyalgia syndrome” since FMS is so much more thanpain with a large number of other distressing symptoms.

Elsewhere, I have argued that differentiation betweenillness and disease is artificial and contrary to patientinterest and hampers proper management of CSS conditions,since anything that is not currently viewed as a disease(i.e., does not have structural pathology, e.g., inflammation,degeneration, or neoplasm) is viewed as predominantly

Pain Research and Treatment 3

Table 1: Prevalence of fibromyalgia syndrome (FMS) in other central sensitivity syndromes (CSS) conditions.

CSS condition∗ % prevalence of FMS (mean) % prevalence of FMS (range) Reference no.

Irritable bowel syndrome 40.7 20.0–65.0 [9, 11–14]Temporomandibular disorder 23.7 13.0–52.0 [9, 15–19]Headaches (all) 26.3 10.0–40.0 [9, 20–23]

Tension-type headache 29.7 23.0–36.4 [9, 23]Migraine 16.0 10.0–22.0 [21, 22]Mixed¶ 38.2 36.4–40.0 [20, 23]

Interstitial cystitis 15.4 12.0–22.4 [9, 24–27]Chronic fatigue syndrome 55.2 15.6–80 [9, 28, 29]Vulvar vestibular syndrome 23.4 15.6–31.2 [30, 31]Gulf War syndrome 17.6 2.0–33.8 [32–34]∗

Prevalence of FMS in other CSS conditions with a single study has been discussed in the text.¶Mixture of tension-type headache and migraine.

although they are present to a lesser extent in other membersof CSS as a manifestation of CS [6].

It was not until 1990s when the presence of FMS in manychronic diseases with structural pathology was generallyrecognized among the researchers. Now, it is knownthat FMS is significantly associated with RA [10, 38–41],systemic lupus (SLE) [42–48], ankylosing spondylitis (AS)[49, 50], osteoarthritis (OA) [51], diabetes mellitus [52, 53],endometriosis [54], hypothyroidism [55], and inflammatorybowel disease [56, 57] (Table 2).

CS alone (without FM) has been reported in juvenilechronic arthritis [59], OA [60–65], endometriosis [66],carpal tunnel syndrome [67–69], chronic pancreatitis [70,71], and Parkinson’s disease [72–74]. It is likely that CSis the harbinger of future development of FMS, as maybe demonstrated in future studies. It is as if “fibro, fibroeverywhere and not a place for the (rational) eyes to hide.”An interesting question is, and data have not emerged yetto answer it, are other members of the CSS family, such asIBS and myogenic TMD also associated with these chronicdiseases with structural pathology?

FMS has been reported also in Sjogren’s syndrome,hepatitis C, HIV, and other infections, for example, Lymedisease. True to the title of this essay, however, only thosediseases that usually cause pain have been described in thispaper.

5. Critical Evaluation of the Studies:Imperfect but the Associations Are Real

A number of studies, both in the category of FMS in CSSand FMS in DWSP, are less than satisfactory because of smallnumbers, unspecified or nonstandard criteria used (both forFMS and the associated diseases), an absence of, or the use ofinappropriate controls as well as inappropriate statistics, forexample, a failure to adjust for multiple comparisons. Lackof blindness, a critical procedure to avoid bias, was universal,as is the case with most published studies in any disease.

However, reported prevalence rates of FMS in generalwere much higher than that in the general population. Sincethe results of all the studies converge in the same direction,

that is, increased prevalence of FMS compared with study orpopulation controls, it seems proper to conclude that trueassociations of FMS with the diseases discussed exist.

6. Pathophysiological Mechanisms of DiseaseAssociations with FMS: Central SensitizationIs Central

6.1. CS and CSS Conditions. Central and common to CSSdiseases are CS. The pathophysiology of CS has beendiscussed elsewhere [6, 8, 75] and is beyond the scope of thisessay. To be sure, the mechanisms involved in CS are multipleand complex [75]. Some of these mechanisms involve tem-poral summation (windup), long-term potentiation (LTP),heterosynaptic potentiation, a dysfunctional descending paininhibition, and an activation of the descending facilitatorypathway [75]. It is also evident that input in one set ofnociceptive fibers amplifies subsequent response to othernonstimulated noceptive or nonnociceptive fibers (het-erosynaptic potentiation). Such phenomena explain diffusedistribution of pain as well as allodynia.

After many years of research in animal models, humanvolunteers, and chronic pain conditions, several facts haveemerged. While a noxious stimulus at some point in thepast might have initiated increased neuronal sensitivity, nofurther nociceptive stimulus is necessary to perpetuate andsustain a state of hyperalgesia or allodynia. That sustainedpain is no longer nociceptive in nature, provoking somephysicians to take recourse to such derogatory lexicons asneurotics, malingerers, somatizers, and “medically unex-plained symptoms” (read “your symptoms are all in yourhead”). In other cases, following the adequate initial noci-ceptive input, only a very low level of nociceptive stimuluswas needed to maintain the CS [75].

With regards to tender points, it is often stated that theyare subjective (thus there is an issue of secondary gain here),but CS may be elicited by stimuli that do not require patient’ssubjective response and are thus purely objective. Such anobjective “test” is nociceptive spinal flexion reflex that hasbeen demonstrated in several CSS conditions [6]. Usingascending and random paradigms, it has been demonstrated

Pain Research and Treatment 3

Table 1: Prevalence of fibromyalgia syndrome (FMS) in other central sensitivity syndromes (CSS) conditions.

CSS condition∗ % prevalence of FMS (mean) % prevalence of FMS (range) Reference no.

Irritable bowel syndrome 40.7 20.0–65.0 [9, 11–14]Temporomandibular disorder 23.7 13.0–52.0 [9, 15–19]Headaches (all) 26.3 10.0–40.0 [9, 20–23]

Tension-type headache 29.7 23.0–36.4 [9, 23]Migraine 16.0 10.0–22.0 [21, 22]Mixed¶ 38.2 36.4–40.0 [20, 23]

Interstitial cystitis 15.4 12.0–22.4 [9, 24–27]Chronic fatigue syndrome 55.2 15.6–80 [9, 28, 29]Vulvar vestibular syndrome 23.4 15.6–31.2 [30, 31]Gulf War syndrome 17.6 2.0–33.8 [32–34]∗

Prevalence of FMS in other CSS conditions with a single study has been discussed in the text.¶Mixture of tension-type headache and migraine.

although they are present to a lesser extent in other membersof CSS as a manifestation of CS [6].

It was not until 1990s when the presence of FMS in manychronic diseases with structural pathology was generallyrecognized among the researchers. Now, it is knownthat FMS is significantly associated with RA [10, 38–41],systemic lupus (SLE) [42–48], ankylosing spondylitis (AS)[49, 50], osteoarthritis (OA) [51], diabetes mellitus [52, 53],endometriosis [54], hypothyroidism [55], and inflammatorybowel disease [56, 57] (Table 2).

CS alone (without FM) has been reported in juvenilechronic arthritis [59], OA [60–65], endometriosis [66],carpal tunnel syndrome [67–69], chronic pancreatitis [70,71], and Parkinson’s disease [72–74]. It is likely that CSis the harbinger of future development of FMS, as maybe demonstrated in future studies. It is as if “fibro, fibroeverywhere and not a place for the (rational) eyes to hide.”An interesting question is, and data have not emerged yetto answer it, are other members of the CSS family, such asIBS and myogenic TMD also associated with these chronicdiseases with structural pathology?

FMS has been reported also in Sjogren’s syndrome,hepatitis C, HIV, and other infections, for example, Lymedisease. True to the title of this essay, however, only thosediseases that usually cause pain have been described in thispaper.

5. Critical Evaluation of the Studies:Imperfect but the Associations Are Real

A number of studies, both in the category of FMS in CSSand FMS in DWSP, are less than satisfactory because of smallnumbers, unspecified or nonstandard criteria used (both forFMS and the associated diseases), an absence of, or the use ofinappropriate controls as well as inappropriate statistics, forexample, a failure to adjust for multiple comparisons. Lackof blindness, a critical procedure to avoid bias, was universal,as is the case with most published studies in any disease.

However, reported prevalence rates of FMS in generalwere much higher than that in the general population. Sincethe results of all the studies converge in the same direction,

that is, increased prevalence of FMS compared with study orpopulation controls, it seems proper to conclude that trueassociations of FMS with the diseases discussed exist.

6. Pathophysiological Mechanisms of DiseaseAssociations with FMS: Central SensitizationIs Central

6.1. CS and CSS Conditions. Central and common to CSSdiseases are CS. The pathophysiology of CS has beendiscussed elsewhere [6, 8, 75] and is beyond the scope of thisessay. To be sure, the mechanisms involved in CS are multipleand complex [75]. Some of these mechanisms involve tem-poral summation (windup), long-term potentiation (LTP),heterosynaptic potentiation, a dysfunctional descending paininhibition, and an activation of the descending facilitatorypathway [75]. It is also evident that input in one set ofnociceptive fibers amplifies subsequent response to othernonstimulated noceptive or nonnociceptive fibers (het-erosynaptic potentiation). Such phenomena explain diffusedistribution of pain as well as allodynia.

After many years of research in animal models, humanvolunteers, and chronic pain conditions, several facts haveemerged. While a noxious stimulus at some point in thepast might have initiated increased neuronal sensitivity, nofurther nociceptive stimulus is necessary to perpetuate andsustain a state of hyperalgesia or allodynia. That sustainedpain is no longer nociceptive in nature, provoking somephysicians to take recourse to such derogatory lexicons asneurotics, malingerers, somatizers, and “medically unex-plained symptoms” (read “your symptoms are all in yourhead”). In other cases, following the adequate initial noci-ceptive input, only a very low level of nociceptive stimuluswas needed to maintain the CS [75].

With regards to tender points, it is often stated that theyare subjective (thus there is an issue of secondary gain here),but CS may be elicited by stimuli that do not require patient’ssubjective response and are thus purely objective. Such anobjective “test” is nociceptive spinal flexion reflex that hasbeen demonstrated in several CSS conditions [6]. Usingascending and random paradigms, it has been demonstrated

BIRDS OF A FEATHER๏ ME/CFS๏ Fibromyalgia๏ Myofascial Pain Syndrome๏ Migraines ๏ Tension Type Headaches๏ Irritable Bowel Syndrome๏ Interstitial Cystitis๏ Pelvic Pain Syndrome๏ PTSD๏ Non-Cardiac Chest Pain (Costochondritis)๏ Temporomandibular Disorder ๏ Irritable Larynx Syndrome๏ Central Abdominal Pains Syndrome (AKA Functional)๏ Other Pain Syndromes

Fibromyalgia and Overlapping Disorders:The Unifying Concept of Central Sensitivity Syndromes

Muhammad B. Yunus, MD

Semin Arthritis Rheum 36:339-356 2007

CENTRAL SENSITIVITY SYNDROMES

ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome); FM (Fibromyalgia); MCS (Multiple Chemical Sensitivities); CLD (Chronic Lyme Disease); IBS (Irritable Bowel Syndrome); T-T (Tension Type); TMD (Temporomandibular Disorders); POTS (Postural Orthostatic Tachycardia Syndrome); RLS (Restless Leg Syndrome); Others including: irritable larynx syndrome, PTSD (Post Traumatic Stress Syndrome, non-cardiac chest pain (costochondritis), myofascial pain syndrome, and other pain syndromes.

Central Sensitization

CSSMigraines

FM

IBS

ME/CFS

CLDMCS

TMDRLS

POTS

Interstitial Cystitis

Pelvic Pain Syndromes

T-T Headaches

Others

Adapted from Yunus, Semin Arthritis Rheum 36:339-356

Open Access Rambam Maimonides Medical Journal

April 2015 � Volume 6 � Issue 2 � e0020

CLINICAL PSYCHOLOGY IN MEDICINE

Special Issue on the Rambam–Mayo Collaboration Guest Editor: John H. Davidson, M.D., M.A.H.L.

Central Sensitization Syndrome and the Initial Evaluation of a Patient with Fibromyalgia: A Review Kevin C. Fleming, M.D.1* and Mary M. Volcheck, R.N.2

1Assistant Professor of Medicine, College of Medicine; Division of General Internal Medicine, Section of Complementary and Integrative Medicine, and Fibromyalgia and Chronic Fatigue Clinic, Mayo Clinic, Rochester, Minnesota, USA; and 2Nursing in Fibromyalgia/Pain Rehabilitation Center, Mayo Clinic, Rochester, Minnesota, USA

Central Sensitization and Fibromyalgia

Box 1. Diagnoses, Self-diagnoses, and Symptoms that May Suggest Central Sensitization Syndrome (Especially If Copious).

Abdominal bloating Abdominal pain, chronic abdominal pain Adrenal insufficiency (self-diagnosed), adrenal

fatigue Alopecia, hair loss, trichotillomania Anxiety Atypical facial pain Atypical or non-cardiac chest pain Autoimmune disorder (self-diagnosed) Autonomic disorder (self-diagnosed)

Black mold, toxic black mold (self-diagnosed) Brain fog, fibrofog Burning mouth syndrome Burning tongue Candida or chronic yeast infection Chiari malformation Chronic low-back pain Chronic non-specific lightheadedness Chronic pain Chronic pelvic pain Chronic prostatitis Chronic tension or migraine headaches

Chronic testicular or scrotal pain Chronic whiplash-associated disorders Chronic widespread pain Complex regional pain syndrome Delusions of parasitosis Depression or bipolar disorder Dizziness Edema or swelling complaints not evident on

examination Ehlers–Danlos syndrome Fatigue or chronic fatigue Fibromyalgia, myalgic encephalitis

Hormone imbalance Hyperventilation Hypoglycemia (self-diagnosed)

Immune deficiency (self-diagnosed) Interstitial cystitis, painful bladder syndrome Irritable bowel syndrome Joint pains Low testosterone or hypogonadism (with normal

test results) Lupus (self-diagnosed) Lyme disease, chronic Lyme disease (self-

diagnosed) Meniere disease

Morgellons disease (self-diagnosed) Multiple chemical sensitivities Multiple drug allergies or intolerances (self-

diagnosed) Multiple food allergies or intolerances (self-

diagnosed) Myofascial pain syndrome Palpitations Panic disorder, episodes, attacks Pelvic pain, chronic pelvic pain, premenstrual

syndrome Polycystic ovary syndrome

Porphyria (self-diagnosed) Post-deployment syndrome Post-traumatic stress disorder Postural orthostatic tachycardia syndrome (POTS) Pseudotumor cerebri Schamberg disease, soft tissue tumors Sick building syndrome Sjögren syndrome (blamed for multiple

symptoms) Temporomandibular disorders,

temporomandibular joint pain Thyroid disease (with normal test results, usually

self-diagnosed) Tinnitus Vulvodynia, vulvar vestibulitis

CENTRAL SENSITIVITY SYNDROMES VS CENTRAL SENSITIZATION

MUSCULOSKELETAL SECTION

Original Research Article

Efficacy and Safety of Duloxetine onOsteoarthritis Knee Pain: A Meta-Analysisof Randomized Controlled Trials

Pain Medicine 2015; 16: 1373–1385Wiley Periodicals, Inc.

THE 3 P’S OF CENTRAL SENSITIVITY SYNDROMES

๏ Predisposing๏ Genetics & Adverse Childhood Events

๏ Precipitating๏ Stressor: Physical, Infectious, Psychological

๏ Perpetuating๏ Levers for treatment

PERPETUATING...

Depression

Poor Sleep Reduced ActivityOver-exertion

Anxiety Stress

For more information visit www.iom.edu/MECFS

Beyond Myalgic Encephalomyelitis/Chronic Fatigue SyndromeRedefining an Illness

Between 836,000 and 2.5 million Americans suffer from myalgic encephalomyelitis/chronic fatigue syndrome—commonly referred to as ME/CFS. This disease is characterized by profound fatigue, cognitive dysfunction, sleep abnormalities, autonomic manifestations, pain, and other symptoms that are made worse by exertion of any sort. ME/CFS can severely impair patients’ ability to conduct their normal lives. Yet many people struggle with symptoms for years before receiving a diagnosis. Fewer than one-third of medical school curricula and less than half of medical textbooks include information about ME/CFS. Although many health care providers are aware of ME/CFS, they may misunderstand the disease or lack knowledge about how to diagnose and treat it. Such gaps in understanding lead to delayed diagnoses and inappropri-ate management of patients’ symptoms. The Department of Health and Human Services (HHS), the National Insti-tutes of Health, the Agency for Healthcare Research and Quality, the Centers for Disease Control and Prevention, the Food and Drug Administration, and the Social Security Administration asked the Institute of Medicine (IOM) to convene an expert committee to examine the evidence base for ME/CFS. In Beyond Myal-gic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness, the com-mittee proposes new diagnostic criteria that will facilitate timely diagnosis and care and enhance understanding among health care providers and the public. In addition, the committee recommends that the name of the disease be changed—from ME/CFS to systemic exertion intolerance disease (SEID)—to more accu-rately capture the central characteristics of the illness.

Understanding ME/CFSThe primary message of the committee’s report is that ME/CFS is a serious, chronic, complex, systemic disease that often can profoundly affect the lives of

ME/CFS is a serious, chronic, complex, systemic disease that often can profoundly affect the lives of patients.

REPORT BRIEF FEBRUARY 2015

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Real Illness

Annals of Internal Medicine EDITORIAL

Anthony L. Komaroff, MDBrigham and Women's Hospital, Harvard Medical SchoolBoston, Massachusetts

Ann Intern Med. 2015;162:871-872. doi:10.7326/M15-0647

INSTITUTE OF MEDICINE REPORT (IOM) ๏ New name: Systemic Exertion Intolerance Disease (SEID)๏ New criteria

๏ Legitimacy

VO2 MAX

Discriminative Validity of Metabolicand Workload Measurements forIdentifying People With ChronicFatigue SyndromeChristopher R. Snell, Staci R. Stevens, Todd E. Davenport, J. Mark Van Ness

Background. Reduced functional capacity and postexertion fatigue after physicalactivity are hallmark symptoms of chronic fatigue syndrome (CFS) and may evenqualify for biomarker status. That these symptoms are often delayed may explain theequivocal results for clinical cardiopulmonary exercise testing in people with CFS.Test reproducibility in people who are healthy is well documented. Test reproduc-ibility may not be achievable in people with CFS because of delayed symptoms.

Objective. The objective of this study was to determine the discriminative validityof objective measurements obtained during cardiopulmonary exercise testing todistinguish participants with CFS from participants who did not have a disability butwere sedentary.

Design. A prospective cohort study was conducted.

Methods. Gas exchange data, workloads, and related physiological parameterswere compared in 51 participants with CFS and 10 control participants, all women,for 2 maximal exercise tests separated by 24 hours.

Results. Multivariate analysis showed no significant differences between controlparticipants and participants with CFS for test 1. However, for test 2, participantswith CFS achieved significantly lower values for oxygen consumption and workloadat peak exercise and at the ventilatory or anaerobic threshold. Follow-up classificationanalysis differentiated between groups with an overall accuracy of 95.1%.

Limitations. Only individuals with CFS who were able to undergo exercisetesting were included in this study. Individuals who were unable to meet the criteriafor maximal effort during both tests, were unable to complete the 2-day protocol, ordisplayed overt cardiovascular abnormalities were excluded from the analysis.

Conclusions. The lack of any significant differences between groups for the firstexercise test would appear to support a deconditioning hypothesis for CFS symp-toms. However, the results from the second test indicated the presence of CFS-relatedpostexertion fatigue. It might be concluded that a single exercise test is insufficientto reliably demonstrate functional impairment in people with CFS. A second testmight be necessary to document the atypical recovery response and protractedfatigue possibly unique to CFS, which can severely limit productivity in the home andworkplace.

C.R. Snell, PhD, Department ofSport Sciences, University of thePacific, Stockton, California, andWorkwell Foundation, Ripon,California.

S.R. Stevens, MA, WorkwellFoundation.

T.E. Davenport, PT, DPT, OCS,Department of Physical Therapy,University of the Pacific, 3601Pacific Ave, Stockton, CA 95211(USA), and Workwell Foundation.Address all correspondence toDr Davenport at: [email protected].

J.M. Van Ness, PhD, Departmentof Sport Sciences, University of thePacific, and Workwell Foundation.

[Snell CR, Stevens SR, DavenportTE, Van Ness JM. Discriminativevalidity of metabolic and workloadmeasurements for identifyingpeople with chronic fatigue syn-drome. Phys Ther. 2013;93:1484–1492.]

© 2013 American Physical TherapyAssociation

Published Ahead of Print:June 27, 2013

Accepted: June 23, 2013Submitted: October 27, 2011

Research Report

Post a Rapid Response tothis article at:ptjournal.apta.org

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other research using the same proto-col to measure physiologicalresponses in people with CFS.30,31 Amore recent study in which the aer-obic power test was used as an exer-cise challenge to study pain and PEMin people with CFS revealed signifi-cant differences in the peak RER

between the CFS group (X!1.25)and the control group (X!0.98).7

On the basis of accepted criteria forevaluating effort during CPET, a peakRER of greater than 1.10 indicatesexcellent effort, and a peak RER ofless than 1.0 reflects submaximaleffort.8,21 The indication is that the

CFS group was working at or close tomaximal exertion, whereas the con-trol group was not. These data haveimportant implications for physicaltherapists because even low-levelexercise assessments and interven-tions can involve nearly maximalexertion by people with CFS.

Figure 1.Measurements of oxygen consumption (V̇O2) at peak exercise (A) and at the ventilatory threshold (B) in participants with chronicfatigue syndrome (CFS) and control participants during cardiopulmonary exercise test 1 (blue bars) and cardiopulmonary exercisetest 2 (gold bars). Error bars represent 1 standard deviation.

Figure 2.Measurements of workload at peak exercise (A) and at the ventilatory threshold (B) in participants with chronic fatigue syndrome(CFS) and control participants during cardiopulmonary exercise test 1 (blue bars) and cardiopulmonary exercise test 2 (gold bars).Error bars represent 1 standard deviation.

Metabolic and Workload Measurements in Chronic Fatigue Syndrome

November 2013 Volume 93 Number 11 Physical Therapy f 1489 by Eresources Unit Library Processing Unit on May 31, 2015http://ptjournal.apta.org/Downloaded from

















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Day 2: Crash

CHRONIC PAIN: SENSITIVITY SHIFT

ARTHRITIS & RHEUMATISM Vol. 46, No. 5, May 2002, pp 1333–1343

Functional Magnetic Resonance Imaging Evidence ofAugmented Pain Processing in Fibromyalgia

Richard H. Gracely,1 Frank Petzke,2 Julie M. Wolf,3 and Daniel J. Clauw2

Objective. To use functional magnetic resonanceimaging (fMRI) to evaluate the pattern of cerebralactivation during the application of painful pressureand determine whether this pattern is augmented inpatients with fibromyalgia (FM) compared with con-trols.

Methods. Pressure was applied to the left thumb-nail beds of 16 right-handed patients with FM and 16right-handed matched controls. Each FM patient un-derwent fMRI while moderately painful pressure wasbeing applied. The functional activation patterns in FMpatients were compared with those in controls, who weretested under 2 conditions: the “stimulus pressure con-trol” condition, during which they received an amountof pressure similar to that delivered to patients, and the“subjective pain control” condition, during which theintensity of stimulation was increased to deliver asubjective level of pain similar to that experienced bypatients.

Results. Stimulation with adequate pressure tocause similar pain in both groups resulted in 19 regionsof increased regional cerebral blood flow in healthycontrols and 12 significant regions in patients. In-creased fMRI signal occurred in 7 regions common toboth groups, and decreased signal was observed in 1common region. In contrast, stimulation of controls

with the same amount of pressure that caused pain inpatients resulted in only 2 regions of increased signal,neither of which coincided with a region of activation inpatients. Statistical comparison of the patient and con-trol groups receiving similar stimulus pressures re-vealed 13 regions of greater activation in the patientgroup. In contrast, similar stimulus pressures producedonly 1 region of greater activation in the control group.

Conclusion. The fact that comparable subjectivelypainful conditions resulted in activation patterns thatwere similar in patients and controls, whereas similarpressures resulted in no common regions of activationand greater effects in patients, supports the hypothesisthat FM is characterized by cortical or subcorticalaugmentation of pain processing.

Fibromyalgia (FM) is characterized by chronicwidespread pain (involving all 4 quadrants of the body aswell as the axial skeleton) and diffuse tenderness (1).Population-based studies have demonstrated that FMaffects !2–4% of the population, with a very similarprevalence in at least 5 industrialized countries (2,3).The etiology of FM remains elusive, although there issupport for the notion that altered central pain process-ing is a factor in the presentation of this disease. Thedevelopment of functional brain imaging techniquesprovides an opportunity to examine central pain pro-cessing in patients with FM.

Although the clinical diagnosis of FM is based ondetecting 11 of 18 tender points (regions that are painfulwhen manually palpated with 4 kg of pressure), in-creased sensitivity to pressure in this condition extendsbeyond tender points and involves the entire body (4–7).In aggregate, psychophysical studies demonstrate thatpatients with FM and control subjects generally detectsensory stimulation (electrical, thermal, mechanical) atthe same levels, but the level at which these stimulibecome unpleasant or noxious (pain threshold) is lowerin patients (8–11).

Supported in part by the National Fibromyalgia ResearchAssociation, by Department of Army grant DAMD 17-00-2-0018, andby the National Institute of Dental and Craniofacial Research, Divi-sion of Intramural Research.

1Richard H. Gracely, PhD: National Institute of Dental andCraniofacial Research, NIH, Bethesda, Maryland, and GeorgetownChronic Pain and Fatigue Research Center, Georgetown University,Washington, DC; 2Frank Petzke, MD, Daniel J. Clauw, MD: George-town University Medical Center, and Georgetown Chronic Pain andFatigue Research Center, Georgetown University, Washington, DC;3Julie M. Wolf, BA: National Institute of Dental and CraniofacialResearch, NIH, Bethesda, Maryland.

Address correspondence and reprint requests to Daniel J.Clauw, MD, University of Michigan Medical Center, 5510 MSRB I,Ann Arbor, MI 48109.

Submitted for publication May 17, 2001; accepted in revisedform December 19, 2001.

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ARTHRITIS & RHEUMATISM Vol. 46, No. 5, May 2002, pp 1333–1343

Functional Magnetic Resonance Imaging Evidence ofAugmented Pain Processing in Fibromyalgia

Richard H. Gracely,1 Frank Petzke,2 Julie M. Wolf,3 and Daniel J. Clauw2

FIBROMYALGIA

๏ Excessive sensory innervation to A-V shunts

๏ Blood flow dysregulation

๏ Symptoms

MUSCULOSKELETAL SECTION

Original Research ArticleExcessive Peptidergic Sensory Innervation ofCutaneous Arteriole–Venule Shunts (AVS) in thePalmar Glabrous Skin of Fibromyalgia Patients:Implications for Widespread Deep Tissue Painand Fatigue

Phillip J. Albrecht, PhD,*,† Quanzhi Hou, MD PhD,*,†

Charles E. Argoff, MD,‡ James R. Storey, MD,§James P. Wymer, MD PhD,‡ and Frank L. Rice, PhD*,†

Conclusions. The excessive sensory innervationto the glabrous skin AVS is a likely source of severepain and tenderness in the hands of FM patients.Importantly, glabrous AVS regulate blood flow to theskin in humans for thermoregulation and to othertissues such as skeletal muscle during periods ofincreased metabolic demand. Therefore, blood flowdysregulation as a result of excessive innervation toAVS would likely contribute to the widespread deeppain and fatigue of FM. SNRI compounds mayprovide partial therapeutic benefit by enhancingthe impact of sympathetically mediated inhibitorymodulation of the excess sensory innervation.

bs_bs_banner

Pain Medicine 2013; 14: 895–915Wiley Periodicals, Inc.

REVIEW ARTICLE

The Dermatological Manifestations of Postural TachycardiaSyndrome: A Review with Illustrated Cases

Hao Huang1 • Anna DePold Hohler1

Am J Clin Dermatol

DOI 10.1007/s40257-015-0144-6

Fig. 1 Evanescent hyperemiamanifesting on the upper chest(a) and lower neck (b) of apatient with posturaltachycardia syndrome

REVIEW ARTICLE

The Dermatological Manifestations of Postural TachycardiaSyndrome: A Review with Illustrated Cases

Hao Huang1 • Anna DePold Hohler1

Am J Clin Dermatol

DOI 10.1007/s40257-015-0144-6

Fig. 1 Evanescent hyperemiamanifesting on the upper chest(a) and lower neck (b) of apatient with posturaltachycardia syndrome

Fig. 2 Raynaud’s phenomenon in a patient with postural tachycardiasyndrome. Note the change in plantar and digital skin colors froma (during the episode) to b (resolved, 3 min after a). Flares ofRaynaud’s phenomenon in this particular patient are exacerbated bycold exposure

Fig. 3 Livedo reticularis in a patient with postural tachycardiasyndrome. Livedo reticularis improved upon administration ofmidodrine

ME/CFS: COMPLEX CHRONIC DISEASE๏ COMT polymorphism & IgG subclass๏ Over 12,600 epigenetic modifications levels๏ fMRI evidence of pain amplification๏ Microbiome disruption๏ Immunologic changes

๏ Low natural killer cell cytotoxicity

๏ Increased activated T lymphocytes

๏ Increased circulating cytokines

๏ Sympathetic Nervous System dysregulation๏ NMDA receptor activation & Gaba depletion๏ Free radicals / oxidative stress

FM & ME/CFSPRIMARY CARE TOOLKIT

Case1

๏ 36female๏ MotorvehiclecollisionJan2008–softtissueinjures๏ Neck/shoulder/upperbackpain๏ Intermittentparesthesiashandandarms&“lightning"paininlegs๏ SeenbyNeurology-MRINormal,EMGNormal–?Somatiform๏ Painnowwidespread–neckbackandshouldersmostbothersome๏ Fatigue,headaches,insomnia,lightheaded,nightsweats๏ IBSsymptomsworse๏ Decreasedmemory,informationoverload๏ Lightandsoundsensitivity

๏ PMH๏ PTSD๏ IrritableBowelSyndrome

๏ AdverseChildhoodevents(ACE);abuse/traumainchildhood

ME/CFS and FM Toolkit Assessment Tool: Diagnosis, Management, and Plan

Recommended Initial Patient Work-up Patient Copy of Plan PATIENT HANDOUT 1 - CSS one-page summary PATIENT HANDOUT 2 - BC Women’s Website PATIENT HANDOUT 3 - Pacing & Self-Management of CFS & FM PATIENT HANDOUT 4 - Anti-inflammatory diet PATIENT HANDOUT 5 - Sleep hygiene instructions Medication and Treatment Handouts Slides from presentation/workshop

COMPLEX CHRONIC DISEASES PROGRAM

Page 1

Baseline Testing and Evaluation of Patients

x ME/CFS, FM, and related disorders are not diagnoses of exclusion and do NOT require an exhaustive workup

x Patient require an appropriate but limited workup to make a diagnosis x Using pre-printed diagnostic criteria checklist can be helpful x Initial evaluation should include:

o History o physical examination o Limited medical work-up o Age-appropriate malignancy screening o OSA screen (e.g., STOP BANG questionnaire)

x The initial evaluation provides a differential diagnosis and identifies possible co-existing conditions that need to be ruled-out (e.g., 50 year-old male patient with FM and significant chest pain also needs a cardiac workup)

x Major categories in the differential diagnosis include: o Malignancy o Infection o Endocrine o Connective Tissue Disease o Psychiatric

Screening blood work

x CBC + diff x Lytes, urea, creatinine x Mg, Phos, Ca x Fasting blood sugar x CRP x Liver tests: AST, ALT, GGT, ALP, bilirubin, albumin x CK x TSH x Ferritin x Urinalysis x HIV x HBV x HCV x FIT test

Note: ANA is not recommended as a screening test Based on the initial evaluation, other testing may be considered but is not usually required

Fibromyalgia and Chronic Fatigue Syndrome Treatment Plan Date: REFERRAL TO THE COMPLEX CHRONIC DISEASES PROGRAM (CCDP) AT BC WOMEN’S HOSPITAL

Already on CCDP wait list Refer to the CCDP.

Please note: the wait list is 1 ½ to 2 years. You will receive a letter from the CCDP once your referral has been received. EDUCATION

Central Sensitivity Syndromes 1-page summary: HANDOUT 1

Education is a major component for coping with these chronic illnesses. See web-based resources at BC Women’s Hospital: HANDOUT 2 bcwomens.ca / Health Info / Living with Illness Living with Complex Chronic Disease / Helpful Resources FAMILY & FRIENDS EDUCATION SESSION

Because this is an invisible illness that is difficult to understand, you, your family, and your friends are invited to participate in a 2-hour family and friends’ session. The session is offered about five time per year in person in Vancouver. Once a year (spring) it is offered as a by webinar.

To register contact: [email protected]

PACING

Pacing and living inside one’s energy envelope are the foundation of self-management and treatment. See web-based resources to learn about these: HANDOUT 3. GROUP

Consider doing an on-line group through the CFIDS & Fibromyalgia Self-Help web site: www.cfidsselfhelp.org/online-courses

Fibromyalgia and Chronic Fatigue Syndrome Treatment Plan Date:

Secondary pain generators that need to be worked up or treated:

Neck

Right hip orbuttocks

Rightupper arm

Chest orbreast

Lower back

Upper backRight Shoulder

Left jawRight jaw

Left Shoulder

Abdomen

Leftupper arm

Rightlower arm

Leftlower arm

Left lower leg

Let hip orbuttocks

Left upper legRight upper leg

Right lower leg

Region 2Region 1

Region 4

Region 3

Region 5

Generalized Pain Total (maximum 5) _____

2016 Revised Fibromyalgia Diagnostic Criteria Seminars in Arthritis and Rheumatism 46 (2016) 319 - 329

Widespread Pain Index (WPI score range 0 - 19)Pain and tenderness during the past week

2 Generalized pain - do not count jaws, chest, or abdomenSymptom Severity Score (SSS score range 0 - 12)Over the past week:No problemSlight or mild problem: genrally mild or intermittentModerate problem: considerable problems; often present and/or at a moderate levelSevere problem: continuous, life-disturbing• Fatigue• Trouble thinking or remembering• Waking up tired (unrefreshed)During the past 6 months:• Pain or cramps in the abdomen• Depression• HeadacheSymptom Severity Score Total (maximum 12) _____

1

3

All of the following criteria must be met to make a diagnosis of Fibromyalgia1. WPI ≥ 7 and SSS ≥ 5 OR WPI 4 to 6 and SSS ≥ 92. Generalized pain: at least 4/5 regions3. Have the symptoms in section 3 and pain been present at a similar clinical level for at least 3 months? Fulfills all diagnostic criteria for FM

Widespread Pain Index Total (maximum 19) _____

No = 0No = 0No = 0

Yes = 1Yes = 1Yes = 1

= 0= 0= 0

= 1= 1= 1

= 2= 2= 2

= 3= 3= 3

No problem Slight/mild SevereModerate

No Yes

No Yes

No Yes

No Yes

ME/CFS: 2003 Canadian Clinical Working Case Definition

Pathological Fatigue A significant degree of new onset, unexplained, persistent or recurrent

physical and/or mental fatigue that substantially reduces activity levels and which is not the result of ongoing exertion and is not relieved by rest

Post-exertional Malaise and Worsening of Symptoms

Mild exertion or even normal activity is followed by malaise: the loss of physical and mental stamina and/or worsening of other symptoms. Recovery is delayed, taking more than 24 hours

Sleep Dysfunction

Sleep is un-refreshing: disturbed quantity - daytime hypersomnia or nighttime insomnia and/or disturbed rhythm - day/night reversal.

Rarely, there is no sleep problem.

Pain Pain is widespread, migratory or localized: myalgia; arthralgia (without

signs of inflammation); and/or headache - a new type, pattern or severity. Rarely, there is no pain

Neurocognitive Manifestations (2 or more)

confusion impaired concentration short-term memory disorientation categorizing and word retrieval perceptual and sensory disturbances ataxia muscle weakness fasciculation cognitive overload emotional overload hypersensitivity to light or sound

At least one symptom from three of the following categories: Autonomic Manifestations orthostatic intolerance–neurally mediated hypotension (NMH) postural orthostatic tachycardia syndrome (POTS) delayed postural hypotension light-headedness extreme pallor nausea and IBS urinary frequency and bladder dysfunction palpitations with or without cardiac arrhythmias exertional dyspnea. . Neuroendocrine Manifestations loss of thermostatic stability–subnormal body temp; marked diurnal

fluctuation sweating episodes recurrent feelings of feverishness cold extremities intolerance heat and cold marked weight change anorexia or abnormal appetite loss of adaptability and worsening of symptoms with stress Immune Manifestations tender lymph nodes recurrent sore throat recurrent flu-like symptoms general malaise new sensitivities to food, medications and/or chemicals.

The illness has persisted for at least 6 months

SEID: 2015 Institute of Medicine Diagnostic Criteria Diagnosis requires the following three symptoms:

A substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities, that persists for more than 6 months and is accompanied by Fatigue, which is often profound, is of new or definite onset (not lifelong), is not the result of ongoing excessive exertion, and is not substantially alleviated by rest, and

Post-exertional Malaise*

and

Unrefreshing Sleep* At least one of the two following:

Cognitive Impairment* or

Orthostatic Intolerance

* Frequency and severity of symptoms should be assessed. The diagnosis of ME/CFS/SEID should be questioned if patients do not have these symptoms at least half of the time with moderate, substantial, or severe intensity.

Other Central Sensitivity Syndromes (CSS):

None

Headaches (tension type) IBS (irritable bowel syndrome) Interstitial Cystitis Irritable larynx syndrome Migraines Myofascial pain syndrome Non-cardiac chest pain Pelvic pain syndrome & related disorders POTS (postural orthostatic tachycardia syndrome PTSD (post-traumatic stress disorder) Restless leg syndrome Temporomandibular disorders Other:

Diet:

Food sensitivities Food allergies

Sleep:

No issues identified Problems with sleep: Initiation Yes No Maintenance Yes No Nightmares Yes No Un-refreshing sleep Yes No Sleep reversal Yes No

Medications tried in the past: Option to try/change On No benefit Couldn’t tolerate/side effects

Gabapentin

Pregabalin (Lyrica)

Topiramate (Topamax)

Beta-blockers

Nabilone (Cesamet)

Nabiximols (Sativex)

Medicinal cannabinoids (dispensary/grey market)

Medicinal cannabinoids (legal supplier)

Cyclobenzaprine (Flexeril)

Dicetel (Pinaverium)

Elmiron

Modafinil

NSAIDS

Opioids

SSRI:

Duloxetine (Cymbalta)

Venlafaxine (Effexor)

Other SNRI:

Tramadol / Tramacet

Triptans:

Amitriptyline

Nortriptyline

Other TCA:

Low Dose Naltrexone:

Other:

Other:

Other:

Sleep

Zopiclone (Imovane)

Zolpidem (Sublinox)

Trazodone

Methotrimeprazine (Nozinan)

Quetiapine (Seroquel)

Mirtazapine (Remeron)

Benzodiazepines:

PLAN REFERRAL TO THE COMPLEX CHRONIC DISEASES PROGRAM (CCDP) AT BC WOMEN’S HOSPITAL

Patient already on wait list Refer (referral form on last 2 pages)

Please note that the wait list is 1 ½ to 2 years. Patient will receive a letter confirming the referral has been received. EDUCATION

One page summary explaining CSS: HANDOUT 1

Education is a major component for coping with these chronic illnesses. Direct the patient to web-based resources at BC Women’s Hospital: HANDOUT 2 FAMILY & FRIENDS EDUCATION SESSION

Because this is an invisible illness that is difficult to understand, invite the patient, their family, and their friends to participate in a 2 hour family and friends’ session. Offered 4 – 5 time per year in person in Vancouver. Once a year (spring) by webinar. To register contact: [email protected] PACING

Pacing and living inside one’s energy envelope are the foundation of self-management and treatment. Direct the patient to web-based resources to learn about these: HANDOUT 3 GROUP

Direct the patient to an on-line group to learn about self-management: www.cfidsselfhelp.org/online-courses DIET

Low inflammatory diet to help with pain: HANDOUT 4

Dietician: Jennifer Hasiuk: [email protected] Skype/phone appointments (not covered by MSP)

Low FODMAPs to help with IBS • See BC Women’s website: recommended websites for IBS IBS:

Probiotic (with bifidobacterium, e.g., Align): 1 tab per day available OTC IBS-C:

Psyllium (e.g., Metamucil); start ½ – 1 tbsp daily; increase to TID as tolerated; provide information sheet

�

WhatareCentralSensi.vitySyndromes?

Centralsensi,vitysyndromes(CSS)belongtoafamilyofsyndromesthatsharethecommonmechanismof“centralsensi,za,on.”Centralmeanstheproblemisatthelevelofthebrainandspinalcord.Theneurons(brainandspinalcordcells)are“hyper-excitable”orsensi,zedbecauseofchangesinthewaythecellscommunicatechemicallyandthroughothermechanisms.Thesensi,zedcellsamplify,ormakestronger,messagesthatwegetfromoursenses(forexampletouchcanfeellikepain,normalligh,ngorsoundcanbeexperiencedasuncomfortable).Butthecellsarenotjustsensi,zed;theyoIensend“wrong”informa,onaswell,andtheycanalsotriggerabnormalresponsestotheenvironment.Forinstancethecellscansendinforma,ontomakeyourheartrace,makeyoufeeldizzy,ornotregulateyourbodytemperaturenormally.Newsensi,vi,estofood,chemicals,andmedica,onscanalsooccur.

WhatareexamplesofCentralSensi.vitySyndromes?

ThediagrambelowshowssomeofthecommonCentralSensi,vitySyndromes.

ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome); FM (Fibromyalgia); MCS (Multiple Chemical Sensitivities); CLD (Chronic Lyme Disease); IBS (Irritable Bowel Syndrome); T-T (Tension Type); TMD (Temporomandibular Disorders); POTS (Postural Orthostatic Tachycardia Syndrome); RLS (Restless Leg Syndrome); Others including: irritable larynx syndrome, PTSD (Post Traumatic Stress Syndrome, non-cardiac chest pain (costochondritis), myofascial pain syndrome, and other pain syndromes.

Central Sensitization

CSSMigraines

FM

IBS

ME/CFS

CLDMCS

TMDRLS

POTS

Interstitial Cystitis

Pelvic Pain Syndromes

T-T Headaches

Others

1

2 3 4

5

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Managing Chronic Fatigue Syndrome andFibromyalgia

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The revised and expanded edition of our introductory course textbook. Readit online for free or purchase it in our Store.

ForewordIntroduction1. Chronic Fatigue Syndrome and Fibromyalgia2. Your Unique Circumstances3. Symptoms of CFS and Fibromyalgia4. Treating Sleep5. Strategies for Pain6. Fighting Fatigue7. Treating Cognitive Problems8. Finding Limits: The Energy Envelope9. Pacing Strategies10. The Pacing Lifestyle11. Achieving Consistency12. Travel and Other Special Events13. Minimizing Relapses14. Pacing Success Stories15. Job Options16. Exercise17. Nutrition and Chemical Sensitivity18. Controlling Stress19. Addressing Feelings20. Eight Ways to Improve Relationships21. Family Issues22. Couples Issues23. How Family and Friends Can Help24. Building a Support Network25. Finding and Working with Doctors26. Grieving Your Losses27. Creating a New Life28. Becoming a Self-Manager29. Goals and Targets30. Logs, Worksheets and Rules31. New Thoughts and New Habits

Foreword

Copyright | Disclaimer | Privacy Policy Site Map | Contact Us

1. www.cfidsselfhelp.org

2.

3.

4.

*

*****

*

Processed & Fried Foods………………………..

Healthy Lifestyle Habits………………………….

Meats & Alternatives……………………………..

Grain Products & Starchy Vegetables..........

Fruits & Non-Starchy Vegetables……….......

Proper Hydration……………..……………………

Dairy & Alternatives………………………………

CCDP’s Anti-Inflammatory Food Guidelines

Limit

Include

2-3 Servings/day

6 Servings/day

6-10 Servings/day

1.5-3 Litres/day

2-3 Servings/day

POTS:

Salt: 9 g (1 tsp) per day; ¼ tsp QID in 1 cup of liquid; provide handout

TRIGGER POINT INJECTIONS

To help with pain:

Muscle MD Clinic (Vancouver): musclemd.ca

Myo Clinic (Victoria): www.myoclinic.ca

Refer locally if available

IMS is an alternative but not covered by MSP

SUPPLEMENTS

NONE suggested (+/- reason):

CFS & FM:

Co-enzyme Q 200 mg TID

D-Ribose 5 g TID

Magnesium Malate 250 mg QID

NADH 10 – 20 mg daily

Vitamin D 2000 IU daily

Other:

IBS bloating and pain:

Iberogast (STW 5): 20 drops three times daily (before or during meals)

Enteric-coated oil of peppermint: 200 – 250 mg BID (depending on brand)

SLEEP

Sleep hygiene: HANDOUT 5

Melatonin: start with 1 - 3 mg, 2-3 hrs before bed (Max: 5 – 10 mg)

Sleep Medication

Trazodone: 50 mg tab; start ¼ to ½ tab; titrate up by ¼ to ½ tab increments to 3 tab (150 mg) qhs as needed;

90 tabs with 3 repeats;

Quetiapine: 25 mg; start ½ tab; titrate up by ½ tab increments to 4 tab (100 mg) qhs as needed;

60 tabs with 3 repeats

Nozinan: 2 mg tabs; start 1 tab 2 hrs before bed; increase by 1 tab increments to 6 mg as needed;


Clonidine: 0.1 mg tabs; 1 – 2 tabs qhs; 60 tabs with 3 repeats

Zopiclone: 5 mg tabs; start ½ tab; titrate up by ½ tab increments to 1.5 tab (7.5 mg) qhs as needed;


Zolpidem: 5 mg tabs; start ½ tab; titrate up by ½ tab increments to 2 tab (10 mg) qhs as needed;


Medication information and dose adjustment handout given to patient

MEDICATIONS

Patient prefers a non-pharmacologic approach

SLEEP HYGIENE INSTRUCTIONS

Adapted from “The Diagnosis of Primary Insomnia and Treatment Alternatives,”

� Sleep only as much as you need to feel refreshed during the following day. Restricting your time in bed helps to consolidate and deepen your sleep. Excessively long times in bed lead to fragmented and shallow sleep. Get up at your regular time the next day, no matter how little you slept.

� Get up at the same time each day, 7 days a week. A regular wake time in the morning leads to regular times of sleep onset, and helps to set your biological clock.

� Exercise regularly. Schedule exercise times so that they do not occur within 3 hours of when you intend to go to bed. Exercise makes it easier to initiate sleep and deepen sleep.

� Don’t take your problems to bed. Plan some time earlier in the evening for working on your problems or planning the next day’s activities. Worrying may interfere with initiating sleep and produce shallow sleep.

� Train yourself to use the bedroom only for sleep and sexual activity. This will help condition your brain to see bed as the place for sleeping. Do not read, watch TV or eat in bed.

� Do not try and fall asleep. This only makes the problem worse. Instead, turn on the light, leave the bedroom, and do something different like reading a book. Don’t engage in stimulating activity. Return to bed only when you feel sleepy.

� Avoid long naps. Staying awake during the day helps to fall asleep at night. Naps totalling more than 30 minutes increase your chances of having trouble sleeping at night.

� Make sure that your bedroom is comfortable and free from light and noise. A comfortable, noise-free sleep environment will reduce the likelihood that you will wake up during the night. Noise that does not awaken you may disturb the quality of your sleep. Carpeting, insulated curtains, and closing the door may help.

� Make sure your bedroom is at a comfortable temperature during the night. Excessively warm or cold sleep environments may disturb sleep.

� Eat regular meals and do not go to bed hungry. Hunger may disturb sleep. A light snack at bedtime (especially carbohydrates) may help sleep, but avoid greasy or heavy foods.

� Avoid excessive liquids in the evening. Reducing liquid intake will minimize the need for night-time trips to the bathroom.

� Cut down on all caffeine products. Caffeinated beverages and food (coffee, tea, cola, chocolate) can cause difficulty falling asleep, awakenings during the night, and shallow sleep. Even caffeine early in the day can disrupt night-time sleep.

� Avoid alcohol, especially in the evening. Although alcohol helps tense people fall asleep more easily, it causes awakenings later in the night.

� Smoking may disturb sleep. Nicotine is a stimulant. Try not to smoke during the night when you have trouble sleeping.

Individual instructions -

……………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………..………

……………………………………………………………………………………………………………………………………..

by M. L. Perlis and S. Youngstead. Comprehensive Therapy 26(4): 298-306, 2000

POTS:

Salt: 9 g (1 tsp) per day; ¼ tsp QID in 1 cup of liquid; provide handout

TRIGGER POINT INJECTIONS

To help with pain:

Muscle MD Clinic (Vancouver): musclemd.ca

Myo Clinic (Victoria): www.myoclinic.ca

Refer locally if available

IMS is an alternative but not covered by MSP

SUPPLEMENTS

NONE suggested (+/- reason):

CFS & FM:

Co-enzyme Q 200 mg TID

D-Ribose 5 g TID

Magnesium Malate 250 mg QID

NADH 10 – 20 mg daily

Vitamin D 2000 IU daily

Other:

IBS bloating and pain:

Iberogast (STW 5): 20 drops three times daily (before or during meals)

Enteric-coated oil of peppermint: 200 – 250 mg BID (depending on brand)

SLEEP

Sleep hygiene: HANDOUT 5

Melatonin: start with 1 - 3 mg, 2-3 hrs before bed (Max: 5 – 10 mg)

Sleep Medication

Trazodone: 50 mg tab; start ¼ to ½ tab; titrate up by ¼ to ½ tab increments to 3 tab (150 mg) qhs as needed;

90 tabs with 3 repeats;

Quetiapine: 25 mg; start ½ tab; titrate up by ½ tab increments to 4 tab (100 mg) qhs as needed;


Nozinan: 2 mg tabs; start 1 tab 2 hrs before bed; increase by 1 tab increments to 6 mg as needed;



Zopiclone: 5 mg tabs; start ½ tab; titrate up by ½ tab increments to 1.5 tab (7.5 mg) qhs as needed;


Zolpidem: 5 mg tabs; start ½ tab; titrate up by ½ tab increments to 2 tab (10 mg) qhs as needed;


Medication information and dose adjustment handout given to patient

MEDICATIONS

Patient prefers a non-pharmacologic approach

Refer locally for medicinal cannabinoids. Discourage the use of grey market dispensaries and compassion clubs

Refer to Dr. MacCallum at the Green Leaf Medical Clinic for medicinal cannabinoids. • Skype visits available. • Info at greenleafmc.ca General

Amitriptyline: 10 mg tabs; start ½ tab 2 hrs before bed; provide patient with dosing schedule; 100 tabs with 3 repeats

Cyclobenzaprine: 10 mg tabs; start ½ tab 2 hrs before bed; provide patient with dosing schedule; 60 tabs with 3 repeats

Nortriptyline: 10 mg tabs; start 1 tab 2 hrs before bed; provide patient with dosing schedule; 150 tabs with 3 repeats

Lyrica: 25 mg tabs; start 1 tab in the evening; provide patient with dosing schedule; 120 tabs with 3 repeats

Gabapentin: 100 mg tabs; start 1 tab in the evening; provide patient with dosing schedule; 200 tabs with 3 repeats

Topiramate: 25 mg tabs; start ½ tab in the evening; provide patient with dosing schedule; 120 tabs with 3 repeats. Provide standing order lab requisition for CBC, lytes (including bicarb), and liver tests: baseline, then q month x 2, then q 6 month

Cymbalta: 30 mg tabs; start 1 tab Q 2 Days; provide patient with dosing schedule; 30 tabs with 3 repeats

Venlafaxine XR: 37.5 mg tabs; start 1 tab daily; provide patient with dosing schedule; 100 tabs with 3 repeats

Nabilone: 0.25 mg tabs; start 1 tab evening/bedtime; provide patient with dosing schedule; 480 tabs dispense 240 at monthly intervals

Naltrexone: 1 mg compounded; start 1 tab daily x 1 wk; 2 mg daily x 1 wk; 3 mg daily x 1 wk; 4mg daily x 1 wk; and 4.5 mg tabs x 1 mo with 3 repeats

Modafinil: 100 mg; start 1 tab daily regular or prn; may increase to 200 mg daily if required; 90 with 3 repeats Iron: ferrous gluconate 300 mg TID; available OTC; you may also want to prescribe PEG 3350 to

prevent constipation (see IBS-C) Iron: ferrous fumarate 300 mg daily; available OTC; you may also want to prescribe PEG 3350 to

prevent constipation (see IBS-C) IBS-D, bloating and pain

Dicetel (pinaverium): 50 mg tabs; start 50 mg TID prn; provide handout; 180 tabs with 3 repeats

Dicyclomine (dicycloverine): 20 mg tabs; start 20 mg QID prn; provide handout; 180 tabs with 3 repeats

Loperamide: 2 mg tabs; 1 – 2 tabs up to 4 times a day; take 45 min AC meals; max 8 tabs (6 mg) per day; available OTC

Cholestyramine: start 4 g per day; provide handout; 100 g NEED TO CHECK AVAILABILITY with 3 repeats

Colesevelam: start 625 mg daily; provide handout; 175 tabs with 3 repeats Amitriptyline: see General above Rifamixin: 550 mg three times daily for 14 days

IBS-C

PEG 3350: start 17 g in 1 cup of water daily with meal; provide handout; available OTC Milk of Magnesia: 15 – 30 mL (1 – 2 tbsp) qhs prn for rescue; provide handout; available OTC SNRI: Cymbalta or venlafaxine XR; see General above

Migraine: Acute treatment

Ibuprofen: 400 – 800 mg; max 1200 mg/day; available OTC Naproxen sodium: 250 – 1000 mg; max 1000 mg/day; 50 tabs with 3 repeats Diclofenac: 50 – 100 mg; max 150 mg/day; 50 tabs with 3 repeats Metoclopramide: 10 – 40 mg Q4-6h; 50 tabs with 3 repeats Rizatriptan: 5 – 10 mg at onset; may repeat dose after 2 hrs; max 20 mg/day; 20 tabs with 3 repeats Zolmitriptan: 2.5 – 5 mg at onset; may repeat dose after 2 hrs; max 10 mg/day; 20 tabs with 3 repeats

CCDP Patient Medication and Treatment Handouts

Acupuncture

Amitriptyline

Cholestyramine

Clonidine for Nightmares

Clonidine for POTS

Clonidine for Opioid Taper

Colesevelam

Cyclobenzaprine

Cyclosporin

Cymbalta

Dicetel

Dicyclomine

Doxepin

Elmiron

Fludrocortisone

Frovatriptan

Gabapentin

Hydroxyzine

Iron

Ivabradine

COMPLEX CHRONIC DISEASES PROGRAM

Medication Handout

Amitriptyline (Elavil)

Date: May 15, 2018

Page 1

Medication: Amitriptyline 10 mg What is Amitriptyline? Amitriptyline belongs to a group of medications called tricyclic antidepressants (TCAs) that were first used to treat depression. It works by altering the levels of certain neuro-transmitters in the brain such as noradrenalin and serotonin. They have since been found to be effective for many different uses such as: pain, helping with sleep quality (but is not a sleeping pill), irritable bowel syndrome (with diarrhea), migraine prevention, and interstitial cystitis. Expected Benefit:

• Usually takes several weeks to notice a benefit • You may not notice a benefit until you get to a dose of 25 mg

Watch for possible side effects: This list of side effects is important for you to be aware of; however, it is also important to remember that not all side effects happen to all people. Many of these less serious side effects will improve over the first few days of taking the medications. If you have problems with these side effects talk with your doctor or pharmacist:

• Dry mouth – this is the most common side; the others are much less frequent • Hangover effect – too sleepy in the morning • Blurred vision • Urinary retention, trouble with urination • Tiredness, dizziness that is more than usual • Diarrhea or constipation

Stopping the medication:

• Do NOT stop taking this medication suddenly without asking your doctor – this medication is usually decreased slowly (at higher doses) before it is stopped completely

How to use this medication: • Take this medication with or without food

Dosing Schedule: • Start with 5 mg (½ tablet) 2 hrs before bed • Increase dose according to table below • Many patients can only tolerate 20 or 30 mg • If you don’t have dry mouth or side effects, you can continue slowly increasing

the dose to a maximum of 70 mg • You can stay at a lower dose (stop increasing) if you get side effects (usually dry

mouth). If this happens, you might want to lower the dose by 5 mg.

COMPLEX CHRONIC DISEASES PROGRAM Medication Handout

Amitriptyline (Elavil)

Date: May 15, 2018

Page 2

Take 2 hrs before bed 5 mg For 1 week 10 mg For 2 weeks 15 mg For 2 weeks 20 mg For 2 weeks 25 mg For 2 weeks 30 mg For 2 weeks Most patients can’t tolerate more than 20-30 mg 35 mg For 2 weeks 40 mg For 2 weeks 45 mg For 2 weeks 50 mg For 2 weeks 55 mg For 2 weeks 60 mg For 2 weeks 65 mg For 2 weeks 70 mg Stay at this dose Follow up with clinic before increasing the dose

Drugs and Foods to Avoid: Ask your doctor or pharmacist before using any other medication, including non-prescription medication (over-the-counter medication) and herbal products.

• Avoid alcohol use at the same time • Take 2 hours after potassium, • Don’t use with yohimbine, St John's Wort, 5HTP, chamomile, ginseng, gotu kola,

hawthorn, kava, lemon balm, goldenseal, passion flower, SAMe, valerian Tips:

• If this medication upsets your stomach, try taking it with food • This medication may make your skin sensitive to sunlight. Try to stay out of

direct sunlight and wear protective clothing and a sun block with SPF 15 or higher

• If you experience dry mouth try chewing sugarless gum, taking sips of water or using a saliva substitute

Please contact the Complex Chronic Diseases Program if you have further questions about your medications.

Migraine: Prophylaxis

Propranolol: 10 mg tabs; start 10 mg daily; provide patient with dosing schedule; 120 tabs with 3 repeats

Topiramate: see General above Divalproex: 125 mg tabs; start 125 mg daily; provide patient with dosing schedule;

120 tabs with 3 repeats; provide standing order lab requisition for liver tests: baseline, then q month x 6, then q 6 month; Note: teratogenic – should not be used in women of childbearing age

Amitriptyline: see General above Venlafaxine XR: see General above

Migraine: Perimenstrual

Frovatriptan: 2.5 mg twice daily 2 days before, continuing for 6 days; 25 tabs with 3 repeats Migraine: Perimenopausal

Venlafaxine XR: see general above Hormone Therapy: (Refer to GP for management

POTS

Propranolol: 10 mg tabs; start 10 mg daily; provide patient with dosing schedule; 200 tabs with 3 repeats

Fludrocortisone: 0.1 mg tabs; start ½ tab daily; provide patient handout; 30 tabs with 3 repeats; provide patient with standing order lab requisition for lytes: baseline, then q 2 weeks x 2, then q month x 2, then q 6 month Interstitial Cystitis

Elmiron (pentosan polysulfate): 100 mg TID 1 hour before or 2 hours after meals; provide patient handout; 90 tabs with 3 repeats

Amitriptyline: see General above Hydroxyzine: 50 mg QHS; 30 tabs with 3 repeats Cyclosporine A: start 1.5 mg/kg/day BID; provide patient handout; dispense 1 month supply

with 3 repeats; Provide standing order lab requisition for creatitine: monitor weekly for first 4 weeks of therapy then q6 months Mood Disorder or Anxiety

SNRI: Cymbalta or venlafaxine XR; see General above Other:

Night Sweats


Other: OTHER TREATMENTS NOT COVERED BY MSP

Counselor who specializes in chronic disease management: Meagan Maddocks, Vancouver, 778-887-9665 Occupational therapist who specializes in CFS and FM: Karen Gilbert, Vancouver, (604) 670-5975 Naturopath for help with mitochondrial health: telehealth visits available

Dr. Gaetano Morello • Phone: 604-925-2560 Fax: 604-925-2567 Toll Free: 1-877-925-2560 • www.westvanwellness.com OTHER RECOMMENDATIONS

NONE FOLLOW-UP

TreatmentFM,CFS,andrelateddisorders

๏ PATIENTEDUCATION๏ LevelAevidence๏ Self-management

๏ PHYSICALACTIVITY๏ LevelAevidence๏ Pacingandlivinginsidethe“energyenvelope”

๏ PSYCHOLOGICALANDBEHAVIOURALTHERAPIES๏ LevelAevidence๏ CBT/groups

๏ DIET๏ Emergingevidence;someRCTdata๏ Lowinflammatorydiet/FODMAPdietforIBS

๏ INTERVENTIONS๏ TriggerPointInjections/dryneedling๏ Emergingevidenceandexpertopinion๏ Acupuncture๏ RCTdata

Sleep

๏ Basemedicaltreatmentonsleepproblem(s)๏ Un-refreshingsleep๏ Sleepinitiation๏ Sleepmaintenance๏ Nightmares

๏ SleepHygiene

๏ Melatonin

Sleep

๏ SleepprotocolavailableonBCWHwebsite

๏ Unrefreshingsleep๏ Tendnottotreatthisdirectly

๏ Painmedsmayhelp๏ Tricyclicantidepressants(TCA)๏ Gabapentinoids/topiramate๏ Cyclobenzaprine๏ Cannabinoids

Medications๏ Tricyclics๏ Amitriptyline๏ Nortriptyline๏ Cyclobenzaprine

๏ Anticonvulsants๏ Pregabalin(Lyrica)๏ Gabapentin๏ Topiramate

๏ Musclerelaxants๏ Cyclobenzaprine(Flexeril)

๏ SNRIs๏ Duloxitine(Cymbalta)๏ VenlafaxineXR(Effexor)

Medications

๏ Cannabinoids๏ Nabilone๏ Dronabinol(USA)๏ Naturalmedicinalcannabinoids

๏ LowDoseNaltrexone ๏ NSAIDS

๏ Paindrivers

๏ Opioids๏ Avoid–OpioidInducedHyperalgesia๏ Taperandwithdrawalprotocol

Case1:Medication

๏ 3for1:pain,IBS,sleepmaintenance

๏ Amitriptyline๏ Goodfirstchoice๏ Startlowandgoslow๏ Start5mg๏ 2hrsbeforebed๏ Adjustaccordingtoprotocol/handout

Case2

๏ 54female๏ FM,IBS,Migraines๏ PainunderreasonablecontrolwithLyrica75

mgBID๏ But…gained50lbs๏ Alsoonquetiapine50mgqhsforsleep๏ Andcitalopram20mgdailyfordepression/

anxiety

Case3

๏ 60male๏ Chronicbackpainfromworkinjury19years

ago๏ Numerousinterventionsineffective

๏ L2-3laminectomyin1996๏ Epiduralsteroidinjections๏ Selectivenerverootblocks

๏ Severalmedicationshavehelped,suchasgabapentin,venlafaxine,andnortriptyline

Case3cont’d

๏ MostrecentMRI๏ posteriordiskbulgeswithoutnerverootcompression๏ osteophytesandotherdegenerativechanges

๏ Usesnarcoticsandhasanarcoticcontract๏ Withoutcontractviolationsordoseescalation

๏ Long-actingoxycodone10mgBIDandNSAIDSprn๏ Abouttwiceaspotentasmorphine

๏ Triedcannabis–recommendationofafriend๏ Helpfulforbothpainandsleep

๏ Hewouldlikeforyoutosignamedicalmarijuanacertificateforhim

PHYSICIAN RESOURCEShttp://www.bcwomens.ca/health-professionals/professional-resources/ccdp-clinician-resources

PATIENT RESOURCESwww.bcwomens.ca/health-info/living-with-illness/living-with-complex-chronic-disease

Primary Care Toolkit - bcwomens.ca

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